Women living in regions with high HIV prevalence are at high risk of HIV acquisition in pregnancy and postpartum because they infrequently use condoms, do not know their partner's HIV status, and have biologic changes or changes in their partner's sexual partnerships that increase susceptibility. Oral pre-exposure antiretroviral prophylaxis (PrEP) is an attractive strategy for HIV prevention in pregnancy/postpartum, given its effectiveness and safety. Clinicians and women are using PrEP in pregnancy; in qualitative studies, women, health workers and policy-makers support use of PrEP in pregnancy, but advocate for models of PrEP delivery that ensure women at risk receive PrEP while minimizing unnecessary PrEP use in women not at risk. Targeting PrEP to women at greatest risk of HIV may maximize benefits, minimize potential risks, and optimize cost-effectiveness. We propose a cluster-randomized clinical trial (RCT) in 20 Maternal Child Health (MCH) clinics in western Kenya (10 clinics per arm, 200 women per clinic, 4000 women overall) to compare 2 models of PrEP delivery in pregnancy. Clinics will offer universal PrEP (women self-select) or targeted PrEP (offer to women with high risk score). Leveraging the pre-existing MCH clinic visit schedule will enable programmatically relevant assessment of PrEP uptake, use, and HIV incidence. The outcome of the study will be a model of PrEP delivery in pregnancy that optimizes effectiveness, safety, and cost- effectiveness. Our team has expertise in maternal-child HIV (John-Stewart, Kinuthia), PrEP trials (Baeten, Richardson) partner self-testing (Thirumurthy), economics and qualitative research (Barnabas, O'Malley). We hypothesize that a targeted PrEP model will result in lower HIV incidence, fewer women on PrEP, more 'appropriate' PrEP use, better adherence, more partners on ART, and will be more cost-effective. Our AIMS: AIM 1a. In a cluster-RCT, to compare universal PrEP (offer to all; women self-select PrEP) to targeted PrEP (offer to women with a high risk score incorporating partner HIV self-test data) for outcomes reflecting the balance of PrEP effectiveness and safety: HIV incidence at 9 months postpartum among all women (including those who did and did not receive PrEP) and proportion of women exposed to PrEP. AIM 1b. To compare trial arms for proportion of women 'appropriately' on PrEP (risk factors), PrEP adherence (drug levels) and duration, partners with known HIV status, partners on ART; infant outcomes (growth, birth outcomes). AIM 2. To estimate the incremental cost-effectiveness of targeted PrEP compared to universal PrEP for women during pregnancy and postpartum, per HIV infection and disability-adjusted life-year (DALY) averted. AIM 3. To qualitatively assess barriers and facilitators to adherence, acceptability, and feasibility in universal and targeted PrEP models at the organizational, provider, and individual woman level. Optimized PrEP delivery in pregnancy will contribute to HIV eradication as highly accessed MCH systems can efficiently deliver PrEP to women in a defined limited risk period and expedite male diagnosis and treatment.